5-(heterocyclic alkyl)-6-aryl-dihydropyrimidines

Abstract

This invention is directed to dihydropyrimidine compounds of the following formula:wherein A iswhich are selective antagonists for human alpha1C receptors. This invention is also related to uses of these compounds for lowering intraocular pressure, inhibiting cholesterol synthesis, relaxing lower urinary tract tissue, the treatment of benign prostatic hyperplasia, impotence, cardiac arrhythmia and for the treatment of any disease where antagonism of the alpha1C receptor may be useful. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier.

What is claimed is:  
     
       1. A compound having the structure:                    
       wherein A is                    
       wherein each of Y 1 , Y 2 , Y 3 , Y 4  and Y 5  is independently —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 3 , —OCOR 3 , —COR 3 , —CONHR 3 , —CON(R 3 ) 2 , or —COOR 3 ; or any two of Y 1 , Y 2 , Y 3 , Y 4  and Y 5  present on adjacent carbon atoms can constitute a methylenedioxy group;  
       wherein X is S; O; or NR 3 ;  
       wherein R 1  is —H; —NO 2 ; —CN; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; —N(R 3 ) 2 ; —OR 3 ; —(CH 2 ) p OR 3 ; —COR 3 ; —CO 2 R 3 ; or —CON(R 3 ) 2 ;  
       wherein R 2  is —H; straight chained or branched C 1 -C 7  alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; C 3 -C 10  cycloalkyl-C 1 -C 10 -alkyl, C 3 -C 10  cycloalkyl-C 1 -C 10 -monofluoroalkyl or C 3 -C 10  cycloalkyl-C 1 -C 10 -polyfluoroalkyl; —CN; —CH 2 XR 3 , —CH 2 X(CH 2 ) p NHR 3 , —(CH 2 ) n NHR 3 , —CH 2 X(CH 2 ) p N(R 3 ) 2 , —CH 2 X(CH 2 ) p N 3 , or —CH 2 X(CH 2 ) p NHCXR 7 ; or —OR 3 ;  
       wherein each p is independently an integer from 1 to 7; wherein each n is independently an integer from 0 to 5;  
       wherein each R 3  is independently —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; or C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;  
       wherein R 4  is                    
       where R 4  in the immediately preceding structure is —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl, straight chained or branched C 2 -C 7  alkenyl or alkynyl; or C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl,                    
       wherein Z is C 2 -C 7  alkenylene or alkynylene; CH 2 ; O; CONR 3 ; S; SO; SO 2 ; or NR 3 ;  
       wherein each D is independently CH 2 ; O; S; NR 3 ; CO; or CS;  
       wherein W is C═O; C═NOR 3 ; substituted or unsubstituted phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl or benzyimidazolyl, wherein the phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl or benzyimidazolyl is substituted with —H, —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  monofluoroalkyl, straight chained or branched C 1 -C 7  polyfluoroalkyl, straight chained or branched C 2 -C 7  alkenyl, straight chained or branched C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  monofluorocycloalkyl, C 3 -C 7  polyfluorocycloalkyl, C 3 -C 7  cycloalkenyl, —N(R 3 ) 2 , —OR 3 , —COR 3 , —CO 2 R 3 , or —CON(R 3 ) 2 ;  
       wherein each V is independently O; S; CR 5 R 7 ; C(R 7 ) 2 ; or NR 7 ;  
       wherein each m is independently an integer from 0 to 3; wherein o is an integer from 1 to 3;  
       wherein each R is independently —H; —F; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; —N(R 3 ) 2 ; —NO 2 ; —CN; —CO 2 R 3 ; or —OR 3 ;  
       wherein R 5  is —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; phenyl, thiophenyl, pyridyl, pyrrolyl, furanyl, imidazolyl or indolyl; —COOR 3 , —COR 3 , —CONHR 3 , —CN, or —OR 3 ;  
       wherein each R 6  is independently —H; straight chained or branched C 1 -C 7  alkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7 cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; or —OR 3 ;  
       wherein each R 7  is independently —H; substituted or unsubstituted benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl, wherein the benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl is substituted with —H, —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  monofluoroalkyl, straight chained or branched C 1 -C 7  polyfluoroalkyl, straight chained or branched C 2 -C 7  alkenyl, straight chained or branched C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  monofluorocycloalkyl, C 3 -C 7  polyfluorocycloalkyl, C 3 -C 7  cycloalkenyl, —N(R 3 ) 2 , —OR 3 , —COR 3 , —C 2 R 3 , or —CON(R 3 ) 2 ; substituted or unsubstituted straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; substituted or unsubstituted straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl or cycloalkenyl, wherein the alkyl, monofluoroalkyl, polyfluoroalkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl is substituted with —H, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl; and  
       wherein R 8  is —H; substituted or unsubstituted benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl, wherein the benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl is substituted with —H, —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  monofluoroalkyl, straight chained or branched C 1 -C 7  polyfluoroalkyl, straight chained or branched C 2 -C 7  alkenyl, straight chained or branched C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  monofluorocycloalkyl, C 3 -C 7  polyfluorocycloalkyl, C 3 -C 7  cycloalkenyl, —N(R 3 ) 2 , —OR 3 , —COR 3 , —CO 2 R 3 , or —CON(R 3 ) 2 ; substituted or unsubstituted straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; substituted or unsubstituted straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl or cycloalkenyl, wherein the alkyl, monofluoroalkyl, polyfluoroalkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl is substituted with —H, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl, —N(R 3 ) 2 , —NO 2 , —CN, —CO 2 R 3 , —OR 3 ;                    
       or a pharmaceutically acceptable salt thereof. 
     
     
       2. An (−) enantiomer of the compound of  claim 1 . 
     
     
       3. An (+) enantiomer of the compound of  claim 1 . 
     
     
       4. The compound of  claim 1  having the structure:                    
     
     
       5. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       6. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       7. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       8. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       9. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       10. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       11. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       12. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       13. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       14. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       15. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       16. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       17. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       18. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       19. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       20. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       21. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       22. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       23. The compound of  claim 4 , wherein the compound has the structure:                    
     
     
       24. The compound of  claim 1  having the structure:                    
     
     
       25. The compound of  claim 24  having the structure:                    
     
     
       26. The compound of  claim 25  having the structure:                    
     
     
       27. The compound of  claim 1  having the structure:                    
     
     
       28. The compound of  claim 27  having the structure:                    
     
     
       29. The compound of  claim 27  having the structure:                    
     
     
       30. A compound having the structure:                    
       wherein A is                    
       wherein each of Y 1 , Y 2 , Y 3 , Y 4  and Y 5  is independently —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —OCOR 4 , —COR 4 , —CONHR 4 , —CON(R 4 ) 2 , or —COOR 4 ; or any two of Y 1 , Y 2 , Y 3 , Y 4  and Y 5  present on adjacent carbon atoms can constitute a methylenedioxy group;  
       wherein X is S; O; or NR 4 ;  
       wherein B is —SCH 2 C 6 H 4 OR 4 ; straight chained or branched C 1 -C 7  alkyloxy, monofluoroalkyloxy or polyfluoroalkyloxy; straight chained or branched C 2 -C 7  alkenyloxy or alkynyloxy; C 3 -C 7  cycloalkyloxy, monofluorocycloalkyloxy, polyfluorocycloalkyloxy or cycloalkenyloxy;  
       wherein R 1  is —H; —NO 2 ; —CN; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; —N(R 4 ) 2 ; —OR 4 ; —(CH 2 ) p OR 4 ; —COR 4 ; —CO 2 R 4 ; or —CON(R 4 ) 2 ;  
       wherein R 2  is —H; straight chained or branched C 1 -C 7  alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, monofluoroalkyl or pplyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; C 3 -C 10  cycloalkyl-C 1 -C 10 -alkyl, C 3 -C 10  cycloalkyl-C 1 -C 10 -monofluoroalkyl or C 3 -C 10  cycloalkyl-C 1 -C 10 -polyfluoroalkyl; —CN; —CH 2 XR 4 , —CH 2 X(CH 2 ) p NHR 4 , —(CH 2 ) n NHR 4 , —CH 2 X(CH 2 ) p N(R 4 ) 2 , —CH 2 X(CH 2 ) p N 3 , or —CH 2 X(CH 2 ) p NHCXR 7 ; or —OR 4 ;  
       wherein each p is independently an integer from 1 to 7;  
       wherein each n is independently an integer from 0 to 5;  
       wherein R 3  is                    
       wherein Z is C 2 -C 7  alkylene; CH 2 ; O; CO; CO 2 ; CONR 4 ; S; SO; SO 2 ; or NR 4 ;  
       wherein each D is independently CH 2 ; O; S; NR 4 ; CO; or CS;  
       wherein W is C═O; C═NOR 4 ; substituted or unsubstituted phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl or benzyimidazolyl, wherein the phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl or benzyimidazolyl is substituted with —H, —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  monofluoroalkyl, straight chained or branched C 1 -C 7  polyfluoroalkyl, straight chained or branched C 2 -C 7  alkenyl, straight chained or branched C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  monofluorocycloalkyl, C 3 -C 7  polyfluorocycloalkyl, C 3 -C 7  cycloalkenyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —CO 2 R 4 , or —CON(R 4 ) 2 ;  
       wherein each V is independently O; S; CR 5 R 7 ; C(R 7 ) 2 ; or NR 7 ;  
       wherein each m is independently an integer from 0 to 3;  
       wherein o is an integer from 1 to 3;  
       wherein each R is independently —H; —F; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; —N(R 4 ) 2 ; —NO 2 ; —CN; —CO 2 R 4 ; or —OR 4 ;  
       wherein each R 4  is independently —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;  
       wherein R 5  is —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; phenyl, thiophenyl, pyridyl, pyrrolyl, furanyl, imidazolyl or indolyl; —COOR 4 , —COR 4 , —CONHR 4 , —CN, or —OR 4 ;  
       wherein each R 6  is independently —H; straight chained or branched C 1 -C 7  alkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; or —OR 4 ;  
       wherein each R 7  is independently —H; substituted or unsubstituted benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl, wherein the benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl is substituted with —H, —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  monofluoroalkyl, straight chained or branched C 1 -C 7  polyfluoroalkyl, straight chained or branched C 2 -C 7  alkenyl, straight chained or branched C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  monofluorocycloalkyl, C 3 -C 7  polyfluorocycloalkyl, C 3 -C 7  cycloalkenyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —CO 2 R 4 , or —CON(R 4 ) 2 ; substituted or unsubstituted straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; substituted or unsubstituted straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl or cycloalkenyl, wherein the alkyl, monofluoroalkyl, polyfluoroalkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl is substituted with —H, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl; and  
       wherein R 8  is —H; substituted or unsubstituted benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl, wherein the benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl is substituted with —H, —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  monofluoroalkyl, straight chained or branched C 1 -C 7  polyfluoroalkyl, straight chained or branched C 2 -C 7  alkenyl, straight chained or branched C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  monofluorocycloalkyl, C 3 -C 7  polyfluorocycloalkyl, C 3 -C 7  cycloalkenyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —CO 2 R 4 , or —CON(R 4 ) 2 ; substituted or unsubstituted straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; substituted or unsubstituted straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl or cycloalkenyl, wherein the alkyl, monofluoroalkyl, polyfluoroalkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl is substituted with —H, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl, —N(R 4 ) 2 , —NO 2 , —CN, —CO 2 R 4 , —OR 4 ;                    
       or a pharmaceutically acceptable salt thereof. 
     
     
       31. An (−) enantiomer of the compound of  claim 30 . 
     
     
       32. An (+) enantiomer of the compound of  claim 30 . 
     
     
       33. The compound of  claim 33  having the structure:                    
     
     
       34. The compound of  claim 33  having the structure:                    
     
     
       35. The compound of  claim 30  having the structure:                    
     
     
       36. The compound of  claim 35  having the structure:                    
     
     
       37. The compound of  claim 36  having the structure:                    
     
     
       38. A compound having the structure:                    
       wherein A is                    
       wherein each of Y 1 , Y 2 , Y 3 , Y 4  and Y 5  is independently —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —OCOR 4 , —COR 4 , —CONHR 4 , —CON(R 4 ) 2 , or —COOR 4 ; or any two of Y 1 , Y 2 , Y 3 , Y 4  and Y 5  present on adjacent carbon atoms can constitute a methylenedioxy group;  
       wherein X is S; O; or NR 4 ;  
       wherein B is —SCH 2 C 6 H 4 OR 4 ; straight chained or branched C 1 -C 7  alkyloxy, monofluoroalkyloxy or polyfluoroalkyloxy; straight chained or branched C 2 -C 7  alkenyloxy or alkynyloxy; C 3 -C 7  cycloalkyloxy, monofluorocycloalkyloxy, polyfluorocycloalkyloxy or cycloalkenyloxy;  
       wherein R 1  is —NO 2 ; —CN; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; —N(R 4 ) 2 ; —OR 4 ; —(CH 2 ) p OR 4 ; —COR 4 ; —CO 2 R 4 ; or —CON(R 4 ) 2 ;  
       wherein R 2  is —H; straight chained or branched C 1 -C 7  alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorbcycloalkyl, polyfluorocycloalkyl or cycloalkenyl; C 3 -C 10  cycloalkyl-C 1 -C 10 -alkyl, C 3 -C 10  cycloalkyl-C 1 -C 10 -monofluoroalkyl or C 3 -C 10  cycloalkyl-C 1 -C 10 -polyfluoroalkyl; —CN; —CH 2 XR 4 , —CH 2 X(CH 2 ) p NHR 4 , —(CH 2 ) n NHR 4 , —CH 2 X(CH 2 ) p N(R 4 ) 2 , —CH 2 X(CH 2 ) p N 3 , or —CH 2 X(CH 2 ) p NHCXR 7 ; or —OR 4 ;  
       wherein each p is independently an integer from 1 to 7;  
       wherein each n is independently an integer from 0 to 5;  
       wherein R 3  is                    
       wherein Z is C 2 -C 7  alkylene; CH 2 ; O; CO; CO 2 ; CONR 4 ; S; SO; SO 2 ; or NR 4 ;  
       wherein each D is independently CH 2 ; O; S; NR 4 ; CO; or CS;  
       wherein W is C═O; C═NOR 4 ; substituted or unsubstituted phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazahyl; benzofuranyl or benzyimidazolyl, wherein the phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl or benzyimidazolyl is substituted with —H, —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  monofluoroalkyl, straight chained or branched C 1 -C 7  polyfluoroalkyl, straight chained or branched C 2 -C 7  alkenyl, straight chained or branched C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  monofluorocycloalkyl, C 3 -C 7  polyfluorocycloalkyl, C 3 -C 7  cycloalkenyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —CO 2 R 4 , or —CON(R 4 ) 2 ;  
       wherein each V is independently O; S; CR 5 R 7 ; C(R 7 ) 2 ; or NR 7 ;  
       wherein each m is independently an integer from 0 to 3;  
       wherein o is an integer from 1 to 3;  
       wherein each R is independently —H; —F; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; —N(R 4 ) 2 ; —NO 2 ; —CN; —CO 2 R 4 ; or —OR 4 ;  
       wherein each R 4  is independently —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;  
       wherein R 5  is —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; phenyl, thiophenyl, pyridyl, pyrrolyl, furanyl, imidazolyl or indolyl; —COOR 4 , —COR 4 , —CONHR 4 , —CN, or —OR 4 ;  
       wherein each R 6  is independently —H; straight chained or branched C 1 -C 7  alkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; or —OR 4 ;  
       wherein each R 7  is independently —H; substituted or unsubstituted benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl, wherein the benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl is substituted with —H, —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  monofluoroalkyl, straight chained or branched C 1 -C 7  polyfluoroalkyl, straight chained or branched C 2 -C 7  alkenyl, straight chained or branched C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  monofluorocycloalkyl, C 3 -C 7  polyfluorocycloalkyl, C 3 -C 7  cycloalkenyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —CO 2 R 4 , or —CON(R 4 ) 2 ; substituted or unsubstituted straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; substituted or unsubstituted straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl or cycloalkenyl, wherein the alkyl, monofluoroalkyl, polyfluoroalkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl is substituted with —H, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl; and  
       wherein R 8  is —H; substituted or unsubstituted benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl, wherein the benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl is substituted with —H, —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  monofluoroalkyl, straight chained or branched C 1 -C 7  polyfluoroalkyl, straight chained or branched C 2 -C 7  alkenyl, straight chained or branched C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  monofluorocycloalkyl, C 3 -C 7  polyfluorocycloalkyl, C 3 -C 7  cycloalkenyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —CO 2 R 4 , or —CON(R 4 ) 2 ; substituted or unsubstituted straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; substituted or unsubstituted straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl or cycloalkenyl, wherein the alkyl, monofluoroalkyl, polyfluoroalkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl is substituted with —H, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrrolyl, naphthyl, indolyl, imidazolyl, benzofurazanyl, benzofuranyl, benzimidazolyl, —N(R 4 ) 2 , —NO 2 , —CN, —CO 2 R 4 , —OR 4 ;                    
       or a pharmaceutically acceptable salt thereof. 
     
     
       39. The compound of  claim 30  or  claim 38 , wherein B is —SCH 2 C 6 H 4 OR 4 . 
     
     
       40. A pharmaceutical composition comprising an amount of the compound of  claim 1 ,  30  or  39  effective to treat benign prostatic hyperplasia and a pharmaceutically acceptable carrier. 
     
     
       41. A method of treating a subject suffering from benign prostatic hyperplasia which comprises administering to the subject an amount of the compound of claims  1  or  30  effective to treat benign prostatic hyperplasia. 
     
     
       42. A method of relaxing lower urinary tract tissue which comprises contacting the lower urinary tract tissue with an amount of the compound of claims  1  or  30  effective to relax lower urinary tract tissue.